Evaluation of genetic loci influencing adult height in the Japanese population

Abstract

Adult height is a highly heritable, classic polygenic trait. The recent advent of genome-wide association studies has led to the identification of robust association at common variants influencing the normal variation of height; the number of loci has now risen to 50. The present study tested the potential overlap of height associations at 46 loci that were previously reported in European-descent populations with those among 1530 Japanese subjects and also attempted to replicate the suggestive association signals that were previously reported in East Asians alone. We found a total of 20 independent loci to be significantly (Po0.05) associated with height among the Japanese subjects (Np6814); 19 loci were originally identified in Europeans and the remaining 1 locus (ZFAT) was previously reported in Koreans (P¼3.8Â10 À9 with the Japanese and Korean data combined for ZFAT). Although 41% (19 of 46) of the loci were nominally replicated, a higher proportion of the tested loci seemed to overlap between the Japanese and Europeans; 83% (38 of 46) of the loci showed a concordant direction of association between the two ethnic groups. Despite the substantial inter-population overlap observed in the present study, further investigation is warranted to search for loci with enhanced genetic impacts in East Asians than in Europeans.

Recent progress in the study of the genetics of height

“…The KARE Project genotyped 8,842 South Koreans and identified 15 loci associated with height, including eight loci that had not been previously implicated in height variation (Cho et al 2009;Kim et al 2010). Five of these height loci were also shown to associate with idiopathic short stature in South Koreans, a condition with a prevalence of 1-2% and defined by an adult height of two Other smaller GWA studies in Japanese and Chinese populations have also been reported (Lei et al 2009;Takeuchi et al 2009). Comparisons of the height association results in East Asians and Caucasians are difficult given the marked difference in sample size.…”

ZFAT is essential for endothelial cell assembly and the branch point formation of capillary-like structures in an angiogenesis model

“…This suggests that ZFAT might also play physiological roles in nonimmune-related cells. Recently, genetic variants in ZFAT were reported to be associated with the interferon-beta responsiveness in multiple sclerosis, an inflammatory autoimmune disease of the central nervous system [4], and with adult height in the Japanese and Korean populations [5,6]. These findings suggest that ZFAT might have critical roles in non-immune-related cells involved in human diseases or altered physiological phenotypes.…”

Immune-related zinc finger gene ZFAT is an essential transcriptional regulator for hematopoietic differentiation in blood islands

“…Thus, elucidation of the relation between ZFAT and FLI-1 might lead to a better understanding of the transcriptional network not only in hematopoietic differentiation, but also in immune regulation. Genetic variants in ZFAT were recently reported to be associated with height in the Japanese and Korean populations (49,50), and development of Zfat −/− embryos were impaired by E8.5, suggesting that ZFAT might be involved in development of mesodermal cells; however, molecular functions of ZFAT in embryonic development and mesoderm lineage should await future studies.…”